Gearoid M. McMahon

Incidence, Outcomes, and Comparisons across Definitions of AKI in Hospitalized Individuals

BACKGROUND AND OBJECTIVES At least four definitions of AKI have recently been proposed. This study sought to characterize the epidemiology of AKI according to the most recent consensus definition proposed by the Kidney Disease Improving Global Outcomes (KDIGO) Work Group, and to compare it with three other definitions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a retrospective cohort study of 31,970 hospitalizations at an academic medical center in 2010. AKI was defined and staged according to KDIGO criteria, the Acute Dialysis Quality Initiatives RIFLE criteria, the Acute Kidney Injury Network (AKIN) criteria, and a definition based on a model of creatinine kinetics (CK). Outcomes of interest were incidence, in-hospital mortality, length of stay, costs, readmission rates, and posthospitalization disposition. RESULTS AKI incidence was highest according to the KDIGO definition (18.3%) followed by the AKIN (16.6%), RIFLE (16.1%), and CK (7.0%) definitions. AKI incidence appeared markedly higher in those with low baseline serum creatinine according to the KDIGO, AKIN, and RIFLE definitions, in which AKI may be defined by a 50% increase over baseline. AKI according to all definitions was associated with a significantly higher risk of death and higher resource utilization. The adjusted odds ratios for in-hospital mortality in those with AKI were highest with the CK definition (5.2; 95% confidence interval [95% CI], 4.1 to 6.6), followed by the RIFLE (2.9; 95% CI, 2.2 to 3.6), KDIGO (2.8; 95% CI, 2.2 to 3.6), and AKIN (2.6; 95% CI, 2.0 to 3.3) definitions. Concordance in diagnosis and staging was high among the KDIGO, AKIN, and RIFLE definitions. CONCLUSIONS The incidence of AKI in hospitalized individuals varies depending on the definition used. AKI according to all definitions is associated with higher in-hospital mortality and resource utilization. AKI may be inappropriately diagnosed in those with low baseline serum creatinine using definitions that incorporate percentage increases over baseline.

A Risk Prediction Score for Kidney Failure or Mortality in Rhabdomyolysis

IMPORTANCE Rhabdomyolysis ranges in severity from asymptomatic elevations in creatine phosphokinase levels to a life-threatening disorder characterized by severe acute kidney injury requiring hemodialysis or continuous renal replacement therapy (RRT). OBJECTIVE To develop a risk prediction tool to identify patients at greatest risk of RRT or in-hospital mortality. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 2371 patients admitted between January 1, 2000, and March 31, 2011, to 2 large teaching hospitals in Boston, Massachusetts, with creatine phosphokinase levels in excess of 5000 U/L within 3 days of admission. The derivation cohort consisted of 1397 patients from Massachusetts General Hospital, and the validation cohort comprised 974 patients from Brigham and Womens Hospital. MAIN OUTCOMES AND MEASURES The composite of RRT or in-hospital mortality. RESULTS The causes and outcomes of rhabdomyolysis were similar between the derivation and validation cohorts. In total, the composite outcome occurred in 19.0% of patients (8.0% required RRT and 14.1% died during hospitalization). The highest rates of the composite outcome were from compartment syndrome (41.2%), sepsis (39.3%), and following cardiac arrest (58.5%). The lowest rates were from myositis (1.7%), exercise (3.2%), and seizures (6.0%). The independent predictors of the composite outcome were age, female sex, cause of rhabdomyolysis, and values of initial creatinine, creatine phosphokinase, phosphate, calcium, and bicarbonate. We developed a risk-prediction score from these variables in the derivation cohort and subsequently applied it in the validation cohort. The C statistic for the prediction model was 0.82 (95% CI, 0.80-0.85) in the derivation cohort and 0.83 (0.80-0.86) in the validation cohort. The Hosmer-Lemeshow P values were .14 and .28, respectively. In the validation cohort, among the patients with the lowest risk score (<5), 2.3% died or needed RRT. Among the patients with the highest risk score (>10), 61.2% died or needed RRT. CONCLUSIONS AND RELEVANCE Outcomes from rhabdomyolysis vary widely depending on the clinical context. The risk of RRT or in-hospital mortality in patients with rhabdomyolysis can be estimated using commonly available demographic, clinical, and laboratory variables on admission.

The Evolving Role of mTOR Inhibition in Transplantation Tolerance

The mammalian target of rapamycin (mTOR) plays a key role in the immune response. mTOR inhibitors suppress T cell activation and proliferation and are effective immunosuppressants. Today there is growing interest in their potential role in inducing tolerance after transplantation. mTOR inhibitors induce anergy in naïve T cells, promote the expansion of regulatory T cells, and inhibit the maturation of dendritic cells, thus promoting immunologic tolerance. Here we review the mechanisms by which mTOR inhibitors promote tolerance. We discuss the clinical relevance of these mechanisms and suggest how they might be used in the design of future protocols to induce tolerance.

Biomarkers in Nephrology: Core Curriculum 2013

The clinical assessment and management of patients with known or suspected kidney disease has been aided for decades by biomarkers, a term defined by a National Institutes of Health (NIH) working group as “A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention.” The characteristics of an ideal biomarker are given in Box 1. Historically, the first biomarker of kidney disease was the finding on physical examination of interstitial edema or ascites, a condition termed dropsy, that was not specific to what eventually became recognized as kidney failure but that rather encompassed a number of clinical conditions including congestive heart failure and cirrhosis. More objective biomarkers in the early days of nephrology included the examination of the urine sediment, followed by measurement of the blood urea nitrogen concentration and the serum creatinine concentration.

Current understanding of chemokine involvement in allograft transplantation

Abstract: Multiple studies have demonstrated that chemokines play an essential role in regulating and co‐ordinating the infiltration of leucocytes into allografts. Chemokines are expressed in skin, liver, heart, and kidney allografts following initial engraftment, ischemic injury, viral infection, and acute and chronic rejection. To date, most of our understanding of chemokine biology has been generated from studies of animal models of transplantation and little is known about the role of chemokines in human allograft rejection. Chemokines may play important mechanistic roles in transplant rejection, in the development of graft arteriosclerosis, and in chronic sclerosing cholangiopathy. Furthermore, these molecules may serve as sensitive diagnostic indicators for the analysis of rejection, including chronic rejection or other forms of graft dysfunction. Lastly, it is possible that chemokine‐targeted therapy might become a feasible option for the treatment of allograft rejection.

Mid-Adulthood Risk Factor Profiles for CKD

Early identification of CKD risk factors may allow risk factor modification and prevention of CKD progression. We investigated the hypothesis that risk factors are present ≥30 years before the diagnosis of CKD in a case-control study using data from the Framingham Offspring Study. Patients with incident CKD (eGFR≤60 ml/min per 1.73 m2) at examination cycles 6, 7, and 8 were age- and sex-matched 1:2 to patients without CKD at baseline (examination 5). CKD risk factors were measured at each examination cycle. Logistic regression models, adjusted for age, sex, and time period, were constructed to compare risk factor profiles at each time point between cases and controls. During follow-up, 441 new cases of CKD were identified and matched to 882 controls (mean age 69.2 years, 52.4% women). Those who ultimately developed CKD were more likely to have hypertension (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.23 to 2.51), obesity (OR, 1.71; 95% CI, 1.14 to 2.59), and higher triglyceride levels (OR, 1.43; 95% CI, 1.12 to 1.83) 30 years before CKD diagnosis, and were more likely to have hypertension (OR, 1.38; 95% CI, 1.07 to 1.79), higher triglyceride levels (OR, 1.35; 95% CI, 1.11 to 1.64), lower HDLc (OR, 0.89; 95% CI, 0.81 to 0.97), and diabetes (OR, 2.90; 95% CI, 1.59 to 5.29) 20 years before CKD diagnosis. These findings demonstrate that risk factors for CKD are identifiable ≥30 years before diagnosis and suggest the importance of early risk factor identification in patients at risk for CKD.

Factors in Career Choice among US Nephrologists

BACKGROUND AND OBJECTIVES There is a projected shortage of kidney specialists, and retention of trainees in nephrology is important. Determining factors that result in choosing a nephrology career could inform future strategies to attract nephrology fellows. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS An anonymous, internet-based survey was sent to members of the American Society of Nephrology in June 2009. Respondents answered questions about demographics, training background, and career choices. RESULTS Of the 3399 members, 913 (23%) returned the survey. Mean age was 51.1 ± 10.5 years, and 46.1% were academic nephrologists. In addition, 38.4% of respondents graduated between 2000 and 2009. Interest in nephrology began early in training, with the intellectual aspects of nephrology, early mentoring, and participation in nephrology electives named as the most common reasons in choosing nephrology. Academic nephrologists were more likely to have participated in research in medical school, have a masters degree or PhD, and successfully obtained research funding during training. Academic debt was higher among nonacademic nephrologists. Research opportunities and intellectual stimulation were the main factors for academic nephrologists when choosing their first postfellowship positions, whereas geographic location and work-life balance were foremost for nonacademic nephrologists. CONCLUSIONS These findings highlight the importance of exposing medical students and residents to nephrology early in their careers through involvement in research, electives, and positive mentoring. Further work is needed to develop and implement effective strategies, including increasing early exposure to nephrology in preclinical and clinical years, as well as encouraging participation in research, in order to attract future nephrology trainees.

Development of an outpatient native kidney biopsy service in low-risk patients: a multidisciplinary approach.

Background: In the US, native kidney biopsies are usually inpatient procedures. We developed an outpatient biopsy protocol for low-risk patients and assessed its safety and efficacy. Methods: Patients with an SBP <140 mm Hg and a BMI ≤35 who were not taking anticoagulants, ASA and NSAIDS in the preceding week were included. Biopsies were performed under ultrasound guidance using a 15-gauge needle that changed to a 14-gauge needle during the study. Patients were discharged after 5 h of observation if there were no signs of bleeding. Complications were carefully recorded. Results: Between November 2008 and April 2011, 105 patients underwent outpatient renal biopsies. A 15-gauge needle was used in 43 patients (group A) while a 14-gauge needle was used in 62 (group B). A median of 25 (range 4–64) glomeruli were obtained in group A versus 39 (range 0–107) in group B (p < 0.001). Complications requiring admission for observation occurred in 7 patients (16%) in group A versus 5 patients (8%) in group B (p = 0.22). One patient in group B had bleeding requiring intervention, while all other complications were minor. Nine complications occurred during the observation period, while 3 patients presented >48 h after biopsy. The mean cost per patient for each outpatient biopsy was USD 976 versus USD 5,489 for inpatients. Conclusions: In a selected low-risk population, outpatient renal biopsy is safe with low complication rates and results in significant cost savings relative to elective inpatient biopsies. The use of a 14-gauge biopsy needle resulted in a greater yield of glomeruli without increased complications.

Mid-adulthood cardiometabolic risk factor profiles of sarcopenic obesity.

Midlife and contemporaneous cardiometabolic risk factors associated with sarcopenic obesity were examined.

Length Polymorphisms in Heme Oxygenase-1 and AKI after Cardiac Surgery

Heme oxygenase-1 (HO-1) catalyzes the degradation of heme, which may be involved in the pathogenesis of AKI. Length polymorphisms in the number of GT dinucleotide repeats in the HO-1 gene (HMOX1) promoter inversely associate with HMOX1 mRNA expression. We analyzed the association between allelic frequencies of GT repeats in the HMOX1 gene promoter and postoperative AKI in 2377 white patients who underwent cardiac surgery with cardiopulmonary bypass. We categorized patients as having the short allele (S; <27 GT repeats) or long allele (L; ≥27 GT repeats), and defined AKI as an increase in serum creatinine ≥0.3 mg/dl within 48 hours or ≥50% within 5 days, or the need for RRT. Compared with patients with the SS genotype, patients with the LL genotype had 1.58-fold (95% confidence interval, 1.06 to 2.34; P=0.02) higher odds of AKI. After adjusting for baseline and operative characteristics, the odds ratio for AKI per L allele was 1.26 (95% confidence interval, 1.05 to 1.50; P=0.01). In conclusion, longer GT repeats in the HMOX1 gene promoter associate with increased risk of AKI after cardiac surgery, consistent with heme toxicity as a pathogenic feature of cardiac surgery-associated AKI, and with HO-1 as a potential therapeutic target.